The proposed study is a competitive renewal of the NINR funded study Nursing Management of IBS: Improving Outcomes. Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder characterized by gastrointestinal (GI) discomfort and alterations in bowel pattern. It is estimated that IBS accounts of over 2 million physician visits per year making it the 4th most expensive GI disorder in the U.S. The burden of IBS has been measured in the significant amount of health care resources used and reductions in health related quality of life (HRQOL) in those affected. The 10-17% prevalence of IBS in the U.S. challenges health care providers to develop and test effective therapeutic strategies to enhance patient self management. The current study builds directly on our prior study of a comprehensive self-management (CSM) program that includes cognitive behavioral therapy to reduce GI symptoms and enhance HRQOL in IBS patients. At the same time there is building evidence that probiotics may provide relief for IBS patients via alterations in gut flora. To date, head to head comparison of probiotics with CSM are lacking. The 2 foci of this study are as follows: 1) Test the effectiveness of probiotics and CSM therapy in patients with IBS as compared to a placebo-control group. The primary outcomes will be abdominal pain and HRQOL. 2) Test the relative effectiveness of probiotics compared to CSM in subgroups of patients defined by degree of intestinal inflammation, as measured by fecal calprotectin, intestinal permeability, and serum cytokine levels. 3) Explore whether other characteristics such as genotype, mental health disorders, abuse history, current levels of anxiety and depression, hypothalamic-pituitary-adrenal axis (cortisol), autonomic nervous system balance (heart rate variability), and symptom severity predict which patients will benefit more from probiotics than from CSM and vice versa. The use of both psychologic and physiologic measures will provide information on not only how 2 diverse therapies work but also information on which they might be most effective. The long term goal is to enhance self management of a chronic, and at times, disabling condition. The current study builds directly on our prior study of irritable bowel syndrome (IBS) which used comprehensive self-management to reduce GI symptoms and enhance quality of life. At the same time there is building evidence that probiotics may provide relief via alterations in gut flora. Clinically, the challenge is to identify which treatment is most appropriate for an individual patient.